beta-endorphin and Skin-Neoplasms

Giant basal cell carcinomas (GBCCs), (BCC ≥ 5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect.. To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD).. Case-control study examining clinicopathologic and neuroactive factors (β-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors.. Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more β-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000).. GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuromediators deserves further study.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; beta-Endorphin; Carcinoma, Basal Cell; Case-Control Studies; Enkephalin, Methionine; Female; Humans; Immunohistochemistry; Male; Middle Aged; Prognosis; Retrospective Studies; Serotonin; Skin Neoplasms; Young Adult

Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of μ-opioid peptides, secreted by tumor cells, on anti-tumor immune responses. For this purpose, tumor growth was studied in wild-type and μ-opioid receptor-deficient (MOR-/-) mice injected with B16 melanoma cells. The ability of these cells to produce opioids was studied by Western blots in vitro. Finally, biopsy material from human melanomas was investigated by immunohistochemistry for ß endorphin expression. Injection of B16 melanoma cells, producing endogenous ß endorphin, in the flank of MOR-/- mice revealed a profound reduction in tumor growth, paralleled by a significantly higher infiltration of immune cells into the tumors, when compared to tumor growth after injection of B16 melanoma cells into wild-type mice. Opioids present in B16 cell supernatant significantly reduced the proliferation of normal but not MOR-/- leucocytes. Immunohistochemical analyses of biopsies from human melanoma tissues showed a positive correlation between expression of ß endorphin and tumor progression. Our data provide evidence that μ-opioid peptides may play a major role in cancer progression by modulating immune response. This finding may have implications for the future optimization of immunointerventions for cancer.

Topics: Animals; beta-Endorphin; Disease Progression; Humans; Lymphocytes, Tumor-Infiltrating; Melanoma; Melanoma, Experimental; Mice; Mice, Knockout; Opioid Peptides; Receptors, Opioid, mu; Skin Neoplasms

UV-induced pigmentation (suntanning) requires induction of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion by keratinocytes. alpha-MSH and other bioactive peptides are cleavage products of pro-opiomelanocortin (POMC). Here we provide biochemical and genetic evidence demonstrating that UV induction of POMC/MSH in skin is directly controlled by p53. Whereas p53 potently stimulates the POMC promoter in response to UV, the absence of p53, as in knockout mice, is associated with absence of the UV-tanning response. The same pathway produces beta-endorphin, another POMC derivative, which potentially contributes to sun-seeking behaviors. Furthermore, several instances of UV-independent pathologic pigmentation are shown to involve p53 "mimicking" the tanning response. p53 thus functions as a sensor/effector for UV pigmentation, which is a nearly constant environmental exposure. Moreover, this pathway is activated in numerous conditions of pathologic pigmentation and thus mimics the tanning response.

Topics: alpha-MSH; Animals; Apoptosis; beta-Endorphin; Carcinoma, Basal Cell; Cell Culture Techniques; Cell Line, Tumor; Foreskin; Genes, p53; Humans; Hyperpigmentation; Keratinocytes; Male; Melanocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Pro-Opiomelanocortin; Promoter Regions, Genetic; RNA, Messenger; Skin; Skin Neoplasms; Skin Pigmentation; Transcriptional Activation; Tumor Suppressor Protein p53; Ultraviolet Rays; Up-Regulation

Melanocyte-stimulating hormone (MSH) has been reported to enhance the experimental metastatic behaviour of melanoma cells in the mouse model. alpha-MSH production and MSH receptor (melanocortin 1 receptor gene) expression have been detected in cultured normal human melanocytes and metastasized melanomas. The exact role of MSH in the metastatic behaviour of human melanoma cells is, however, not yet known. To clarify a possible role of proopiomelanocortin (POMC)-derived peptides, including alpha-MSH, in melanoma development and progression, we analysed immunohistochemically the localization of alpha-MSH adrenocorticotrophic hormone (ACTH) and beta-endorphin in various kinds of benign pigmented naevocytic lesions and malignant melanomas. Three of 21 samples of common and dysplastic naevi showed detectable alpha-MSH staining in naevus cells, and five and six of 15 samples were weakly positive for ACTH and beta-endorphin staining, respectively. In melanoma samples, 24 of 45, 23 of 39 and 30 of 42 samples showed positive staining with alpha-MSH, ACTH and beta-endorphin antibodies, respectively. Furthermore, staining for all three antibodies was noted to be more intense and diffuse in samples of nodular melanoma, vertically growing acral lentiginous melanoma and superficial spreading melanoma as well as metastatic lesions compared with those of naevi. Although it is yet to be determined whether or not this strong staining for POMC-derived peptides in advanced melanoma cells indicates a role of autocrine or paracrine regulation, our results suggest a possible involvement of POMC gene products in melanoma progression.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Humans; Immunohistochemistry; Melanocyte-Stimulating Hormones; Melanoma; Nevus, Pigmented; Pro-Opiomelanocortin; Skin; Skin Neoplasms

Topics: Adrenocorticotropic Hormone; alpha-MSH; beta-Endorphin; Carcinoma, Squamous Cell; Cells, Cultured; Chromatography, High Pressure Liquid; Humans; Melanocytes; Melanoma; Skin Neoplasms

We investigated the presence of proopiomelanocortin (POMC) products in sections of skin from normal subjects and patients with neoplastic and non-neoplastic cutaneous disorders. Antibodies specific against adrenocorticotropin, beta-melanotropin, and beta-endorphin were used for detection and characterization of cell types bearing POMC peptides. POMC products were not observed in sections of normal skin from the corporal (non-scalp) areas (six cases), whereas the hair follicles of scalp skin exhibited positive immunostains that were readily apparent (four cases). POMC products were frequently detected in corporal skin affected by diseases (13 of 26 cases), for example, psoriatic keratinocytes, the inflammatory infiltrate in scarring alopecia, nevocytes, the epithelial cell nests of basal cell carcinoma, and melanoma cells. Further tests were performed in keloids, a primary reactive skin disorder, to evaluate whether POMC accumulation represented a disease-related phenomenon or an expression of normal cutaneous reactivity. POMC products were consistently detected (10 of 11 cases) in the keratinocytes and mononuclear cells at keloid lesions. Thus these observations indicate that POMC products may accumulate locally in lesional skin representing, presumably, a novel cutaneous response to injury. The broad spectrum of POMC products detected suggests that these arise from production in situ (expression of the POMC gene itself) by human skin.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Carcinoma, Basal Cell; Cytoplasm; Humans; Immunohistochemistry; Keratinocytes; Melanocyte-Stimulating Hormones; Melanoma; Nevus; Pro-Opiomelanocortin; Psoriasis; Scalp; Skin; Skin Diseases; Skin Neoplasms

Since the initial clinical presentation of visceral neuroendocrine carcinoma is occasionally a cutaneous metastasis, diagnostic confusion with primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma) may ensue. In this study, seven cases of secondary cutaneous neuroendocrine carcinoma were immunohistochemically compared with twenty-one Merkel cell carcinomas for ten antigenic moieties that have been associated with endocrine tumors. Six of seven secondary tumors stained for bombesin, leucine enkephalin, methionine enkephalin, or beta-endorphin, none of which was detected in the primary cutaneous neuroendocrine carcinomas. These data suggest that immunohistochemical study may be useful in separating primary from secondary neuroendocrine tumors of the skin and may assist in directing clinical attention to the most probable site of visceral neoplasia.

Topics: Adult; Aged; beta-Endorphin; Bombesin; Carcinoid Tumor; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Phosphopyruvate Hydratase; Skin; Skin Neoplasms